Stretchable solvent-free ionic conductor with self-wrinkling microstructures for ultrasensitive strain sensor.
Stretchable solvent-free ionic conductors with outstanding physicochemical stability are attractive in emerging sensing devices. However, existing ionic conductors struggle to keep high strain sensitivity with a gauge factor (GF) smaller than 4 at a strain range of up to 100%, which seriously affects the reliability of the signal output. Herein, we prepared a novel solvent-free ionic conductor, consisting of a hybrid cross-linked polymer network and mobile ions. Exquisite reticular wrinkling microstructures with ion channels were formed spontaneously by utilizing modulus mismatch in shrinkage during polymerization. The ion channels promote the ionic transport in the polymer, and the reticular wrinkling microstructures dramatically reinforce the mechanical stability and enhance energy dissipation. After being carefully optimized, the as-prepared ionic conductor demonstrated many unique advantages including perfect physicochemical stability, wide operating temperature range, the high ionic conductivity of 1.17 mS cm-1 at 15 °C and excellent sensitivity with GF as high as 7.03 at 100% strain. Moreover, benefiting from the abundant hydrogen bonds and ionic interactions in the polymer network, the ionic conductor also possesses self-healable and adhesion ability. The resulting devices can be used for quantitative evaluation of human joint motion and exhibit great potential in soft electronics or iontronics.


Topical management of psoriasis - corticosteroids and sparing corticosteroid therapy.
Psoriasis is a complex disease that requires safe, long-term treatment. Topical steroid therapy, topical non-steroid therapy only, and a combination of various topical therapies in the treatment of mild to moderate forms of psoriasis are presented. Topical therapy includes corticosteroids, vitamin D3 analogs, retinoids, tars, anthralin, keratolytics, and topical immunomodulators. While most medications are approved for use as a single agent in the treatment of psoriasis, some of these drugs are most effective when used in combination with topical corticosteroids. Topical therapy is generally administered for mild and localized forms of psoriasis, whereas phototherapy and systemic therapy are reserved for extensive lesions and more severe forms of the disease. Individual approach is absolutely necessary in each patient with psoriasis.


[Nursing education at the university in Brazil: three experiences].
The ways of forming the nursing professional are linked to the history and to the socio-political and economic context. The article discusses the academic training for nurses in Brazil in three different public universities : University of São Paulo, Ribeirão Preto ; Federal University of Goiás, Catalão and Federal University of Minas Gerais, Belo Horizonte. It notes the challenges and their differences and similarities. The networks of health services, the universities and university training for nurses are too much different in Brazilian territory. A national law that regulates the training of nurses but the universities has some autonomy to apply these programs. How this structure the nurses formation in this three different universities that we'll compared ? Even with the resources and different histories, the programs of formation have the objectives the management of integral quality care in all health and social services in the country. The achievement of this project is conditioned in each university to the reality and the situation of the health care system and universities as well the work of the professor and nurses.


Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania.
This study was part of a larger cross-sectional survey that was evaluating tuberculosis (TB) infection in humans, livestock and wildlife in the Serengeti ecosystem in Tanzania. The study aimed at evaluating the genetic diversity of Mycobacterium tuberculosis isolates from TB patients attending health facilities in the Serengeti ecosystem. DNA was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated TB patients aged ≥18 years. Spacer oligonucleotide typing (spoligotyping) and Mycobacterium Interspersed Repetitive Units and Variable Number Tandem Repeat (MIRU-VNTR) were used to genotype M. tuberculosis to establish the circulating lineages. Of the214 M. tuberculosis isolates genotyped, 55 (25.7%) belonged to the Central Asian (CAS) family, 52 (24.3%) were T family (an ill-defined family), 38 (17.8%) belonged to the Latin American Mediterranean (LAM) family, 25 (11.7%) to the East-African Indian (EAI) family, 25 (11.7%) comprised of different unassigned ('Serengeti') strain families, while 8 (3.7%) belonged to the Beijing family. A minority group that included Haarlem, X, U and S altogether accounted for 11 (5.2%) of all genotypes. MIRU-VNTR typing produced diverse patterns within and between families indicative of unlinked transmission chains. We conclude that, in the Serengeti ecosystem only a few successful families predominate namely CAS, T, LAM and EAI families. Other types found in lower prevalence are Beijing, Haarlem, X, S and MANU. The Haarlem, EAI_Somalia, LAM3 and S/convergent and X2 subfamilies found in this study were not reported in previous studies in Tanzania.


Transcriptomic and metabolomic profiles of Chinese citrus fly, Bactrocera minax (Diptera: Tephritidae), along with pupal development provide insight into diapause program.
The Chinese citrus fly, Bactrocera minax (Enderlein), is a devastating citrus pest in Asia. This univoltine insect enters obligatory pupal diapause in each generation, while little is known about the course and the molecular mechanisms of diapause. In this study, the course of diapause was determined by measuring the respiratory rate throughout the pupal stage. In addition, the variation of transcriptomic and metabolomic profiles of pupae at five developmental stages (pre-, early-, middle-, late-, and post-diapause) were evaluated by next-generation sequencing technology and 1H nuclear magnetic resonance spectroscopy (NMR), respectively. A total of 4,808 genes were significantly altered in ten pairwise comparisons, representing major shifts in metabolism and signal transduction as well as endocrine system and digestive system. Gene expression profiles were validated by qRT-PCR analysis. In addition, 48 metabolites were identified and quantified by 1H NMR. Nine of which significantly contributed to the variation in the metabolomic profiles, especially proline and trehalose. Moreover, the samples collected within diapause maintenance (early-, middle-, and late-diapause) only exhibited marginal transcriptomic and metabolomic variation with each other. These findings greatly improve our understanding of B. minax diapause and lay the foundation for further pertinent studies.


High-Risk Pulmonary Embolism: Management for the Intensivist.
High-risk pulmonary embolism (PE) also known as massive PE carries a high rate of morbidity and mortality. The incidence of high-risk PE continues to increase, yet the outcomes of high-risk PE continue to remain poor. Patients with high-risk PE are often critically ill, with complex underlying physiology, and treatment for the high-risk PE patient almost always requires care and management from an intensivist. Treatment options for high-risk PE continue to evolve rapidly with multiple options for definitive reperfusion therapy and supportive care. A thorough understanding of the physiology, risk stratification, treatment, and support options for the high-risk PE patient is necessary for all intensivists in order to improve outcomes. This article aims to provide a review from an intensivist's perspective highlighting the physiological consequences, risk stratification, and treatment options for these patients as well as providing a proposed algorithm to the risk stratification and acute management of high-risk PE.


Posttraumatic stress disorder and treatment seeking in a nationally representative Canadian military sample.
This study aimed to identify predictors of treatment seeking in military members with posttraumatic stress disorder (PTSD) using data from the 2002 Canadian Community Health Survey-Canadian Forces Supplement (Statistics Canada, 2003). To identify predictors, two complementary analyses (binary logistic regression and recursive partitioning of independent variables) were conducted in military members with PTSD (N = 509). Results indicate that trauma-related (index traumatic event type, cumulative trauma exposure), demographic (marital status), enabling (income), and need (PTSD interference) factors predict treatment seeking in military members with PTSD, and that treatment seekers and nontreatment seekers are both comprised of distinct subgroups. Interventions aimed at increasing treatment-seeking behaviors should be tailored to the specific needs of various subgroups of nontreatment seekers.


Exploring the Experiences of Family Members When a Patient Is Admitted to the ICU with a Severe Traumatic Brain Injury: A Scoping Review.
The needs of family members of patients in the intensive care unit (ICU) with a severe traumatic brain injury (TBI) remain unmet. To date, no review has been performed to explore the experiences of relatives of adults who have been admitted to the ICU for treatment of a TBI. The aim of this scoping review is to explore and map the evidence of the experiences of family members when an adult relative is admitted to an ICU with a severe TBI. This review follows a combination of guidelines from Arksey and O'Malley and the Joanna Briggs Institute. Five electronic databases, Medline, Emcare, Embase, CINAHL, and PsycInfo were searched in February 2023, as were a number of grey literature sources. The population, concepts, and context framework were used to define the inclusion and exclusion criteria. From 4077 records, nine studies were retained, which represented seven discrete studies. The experiences of family members were thematically analyzed. The narrative synthesis of findings revealed three themes: communication with the clinical team, uncertainty, and involvement in care. These results offer richness and depth of understanding to clinicians regarding the experiences of families during this traumatic time. This review provides direction for targeted interventions aimed at supporting family members while in the ICU.


Designing sustainable healthcare facilities.
A sustainable approach to the design of healthcare premises is essential if the business effectiveness of facilities is to be maximised through their whole life. This report, by Phil Nedin, president of IHEEM and Arup global healthcare business leader, is based on a paper he presented at this year's annual general meeting of the Institute.


Leptin regulation of inward membrane currents, electrical activity and LH release in isolated bovine gonadotropes.
Leptin, a peptide hormone produced by adipocytes, is recognized as one of the signals involved in the onset of reproductive activity. The leptin receptor has been found in hypothalamic neurons and pituitary gonadotropes, suggesting that the hormone may act at both sites to stimulate the secretion of GnRH and consequently, FSH and LH. In response to a stimulus such as a hypothalamic secretagogue, gonadotropes respond with changes in electrical activity, intracellular Ca2+ and hormone release. The main aim of this report was to investigate whether leptin promotes a change in the electrical and secretory activities of bovine gonadotropes. After 48 h of treatment with leptin (10 nM) significant changes in the action potential properties were observed in gonadotropes, which included an increase in amplitude, time-to-pike and post-hyperpolarization, as well as a decrease in firing threshold. Likewise, leptin induced a significant (∼1.3-fold) up-regulation of voltage-gated Na+ channel current density, and a selective increase (∼2.1-fold) in Ca2+ current density through high voltage-activated channels. Consistent with this, leptin enhanced GnRH-induced secretion of LH measured by ELISA. We suggest that leptin enhances membrane expression of voltage-gated Na+ and Ca2+ channels, which results in a modulation of the action potential properties and an increase in hormone release from gonadotropes.


A multiplex PCR for species- and virulence-specific determination of Listeria monocytogenes.
Listeria monocytogenes internalin gene inlJ has been described previously for differentiation of virulent from avirulent strains. However, a recent report indicated that there exist some unusual lineage IIIB strains (e.g., serotype 7 strain R2-142) that possess no inlJ gene but have the capacity to cause mouse mortality via intraperitoneal inoculation. Therefore, a multiplex PCR incorporating inlA, inlC and inlJ gene primers was developed in this study for rapid speciation and virulence determination of L. monocytogenes. Although inlB gene was also assessed for species-specific recognition, it was not included in the multiplex PCR due to the negative reaction observed between the inlB primers and serotypes 4a-e strains. The species identity of the 36 L. monocytogenes strains under investigation was verified through the amplification of an 800 bp fragment with the inlA primers and the virulence of these strains was ascertained by the formation of 517 bp and/or 238 bp fragments with the inlC and inlJ primers, respectively. Whereas L. monocytogenes pathogenic strains with capacity to cause mortality (showing relative virulence of 30-100%) in A/J mice via the intraperitoneal route were invariably detected by the inlC and/or inlJ primers, naturally non-pathogenic strains (showing relative virulence of 0%) were negative with these primers. While 8 of the 10 L. ivanovii strains reacted with the inlC primers, they could be effectively excluded as non-L. monocytogenes through their negative reactions with the inlA primers in the multiplex PCR. Thus, the use of the multiplex PCR targeting inlA, inlC and inlJ genes facilitates simultaneous confirmation of L. monocytogenes species identity and virulence.


DNA metabarcoding of benthic algae and associated eukaryotes from Lake Baikal in the face of rapid environmental changes.
Here we report new data describing the biodiversity of phytobenthic communities based on DNA-metabarcoding using the 18S rDNA marker and the Illumina MiSeq system. The study was initiated due to the blooming of f ilamentous algae (mainly of the genus Spirogyra) and cyanobacteria in the coastal zone of Lake Baikal under climate change and anthropogenic impact. The composition and taxonomic diversity of algae and other organisms associated with them on different sites of Lake Baikal (near Bolshoi Ushkaniy Island, in Listvennichny Bay) and in the Kaya (within the city of Irkutsk, located in the same drainage basin as Lake Baikal) were determined using DNAmetabarcoding. About 15 thousand reads of the 18S rRNA marker were obtained by applying NGS (next-generation sequencing). The species of algae dominating in the number of reads, as well as the diff icult-to-identify taxa (Stramenopiles, Alveolata, Euglenozoa, Chromista, Rhizaria, Amoebozoa, etc.), which play an important role in the functioning and formation of the structure of algal communities, were revealed. The Shannon index of the communities studied ranges from 1.56 to 2.72. The advantages and weaknesses of using DNA-metabarcoding based on the 18S rRNA gene fragment for studying the structure of algal communities are shown. The advantage of this method is the possibility to more fully determine the diversity of eukaryotes taxa, which are diff icult to identify by morphology, without involving a large number of specialists, while the disadvantage of the method is the distortion that may occur during the PCR. Here, ways of solving this problem are proposed. The results of the study show that the analysis of the minor component of the eukaryotic community in samples (organisms with low biomass) consisting of a mixture of multicellular and unicellular organisms requires a read-depths of at least 100,000 sequences per sample. In general, the DNA-metabarcoding method is recommended for studying the structure of algal communities and eukaryotes associated with them.


Estimation of changes in breech face and firing pin marks over consecutive discharges and its impact on an IBIS® Heritage™ System.
When a firearm is discharged, the individual marks of the breech face and firing pin are imprinted onto the primer of the cartridge case. These individual marks are reproducible between shots; however, over a large number of consecutive shots, it has been observed that minute changes in these individual marks may occur. Changes in individual marks may affect an examiner in their ability to identify or eliminate and may change the magnitude of a likelihood ratio, depending on the system used by the laboratory, but the effect that these changes have on the Integrated Ballistic Identification System (IBIS®) is largely unknown. If such changes negatively affect the performance of the IBIS® then consequences may result with respect to the correct matching candidate not be returned in the top results further compared by an examiner. Two hundred consecutive test fires performed in a clean environment (indoor shooting range) were collected in sequence from 24 new Ruger® SR9 9mm pistols and entered into an IBIS® Heritage™ System. The full known match data were extracted for each firearm, and δ sets were created that had a specific number of cartridge cases between the two cartridge cases being compared. Receiver operating characteristic (ROC) area under the curve (AUC) values for these δ sets were compared to the full known match sets to determine if any significant changes in performance resulted. Although there were instances of significant differences, these only occurred in less than 25% of comparisons, and overall no decreasing trends in performance were observed.


Profiling Total Viable Bacteria in a Hemodialysis Water Treatment System.
Culture-dependent methods, such as heterotrophic plate counting (HPC), are usually applied to evaluate the bacteriological quality of hemodialysis water. However, these methods cannot detect the uncultured or viable but non-culturable (VBNC) bacteria, both of which may be quantitatively predominant throughout the hemodialysis water treatment system. Therefore, propidium monoazide (PMA)-qPCR associated with HPC was used together to profile the distribution of the total viable bacteria in such a system. Moreover, high-throughput sequencing of 16S rRNA gene amplicons was utilized to analyze the microbial community structure and diversity. The HPC results indicated that the total bacterial counts conformed to the standards, yet the bacteria amounts were abruptly enhanced after carbon filter treatment. Nevertheless, the bacterial counts detected by PMA-qPCR, with the highest levels of 2.14 × 107 copies/100 ml in softener water, were much higher than the corresponding HPC results, which demonstrated the occurrence of numerous uncultured or VBNC bacteria among the entire system before reverse osmosis (RO). In addition, the microbial community structure was very different and the diversity was enhanced after the carbon filter. Although the diversity was minimized after RO treatment, pathogens such as Escherichia could still be detected in the RO effluent. In general, both the amounts of bacteria and the complexity of microbial community in the hemodialysis water treatment system revealed by molecular approaches were much higher than by traditional method. These results suggested the higher health risk potential for hemodialysis patients from the up-to-standard water. The treatment process could also be optimized, based on the results of this study.


Actin dynamics and organization during growth cone morphogenesis in Helisoma neurons.
Growth cone formation at the terminal region of severed axons is a fundamental step in neuronal regeneration. To understand the cytoskeletal events underlying this process, we have followed actin organization and dynamics as the severed, axonal stumps of Helisoma neurons transformed into mature growth cones. We identified three stages in growth cone morphogenesis: (1) formation, (2) expansion, and (3) maturation. The formation stage involved cytochalasin B-insensitive terminal swelling formation, followed by cytochalasin B-inhibited filopodial and lamellipodial formation. Time-lapse images of neurons injected with labeled actin showed actin ribs in nascent growth cones formed both by incorporation of filopodial actin bundles and de novo assembly at the leading edge. Phallacidin-stained growth cones revealed F-actin to be organized into bundles (ribs) and a meshwork throughout morphogenesis. Actin ribs represented the dominant F-actin population during the expansion stage and the early phase of maturation, whereas a meshwork organization dominated the late phase of maturation. During the expansion stage, growth cones exhibited a rapid retrograde flow (4.8 microns/min), as assessed with flow-coupled latex beads, and comparatively slow lamellipodial protrusion (0.3 micron/min). During the maturation stage, no net lamellipodial advancement occurred; however, the rate of retrograde flow was significantly faster in the early phase (5.0 microns/min) than the late phase (2.3 microns/min). This decrease in retrograde flow corresponded with a change in actin organization. Lateral movements of actin ribs (2.1 microns/min) also occurred throughout growth cone morphogenesis, but were most prominent during the expansion stage. These experiments provide evidence for de novo actin assembly during growth cone formation and demonstrate that temporal changes in actin organization and dynamics accompany growth cone morphogenesis.


The genetic association between type 2 diabetic and hepatocellular carcinomas.
Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) are both major health problems throughout the world. It has been reported that T2DM is an independent risk factor for HCC, although the pathophysiology is still unclear. In order to identify differentially expressed genes (DEGs) in T2DM and HCC, gene expression datasets for T2DM (GSE15653), HCC (GSE60502) and metformin-treated cells (GSE69850) were obtained from the Gene Expression Omnibus database repository. Protein-protein interaction (PPI) networks for the DEGs were constructed and gene clusters selected for functional enrichment analysis. Ten genes with the highest degree of connectivity were selected as hub genes and prognostic analysis together with analysis of gene expression and protein distribution were performed for these genes. Lastly, we investigated associations between the hub genes and genes associated with metformin treatment in hepatocarcinoma cells. In total, 256 common DEGs, including 155 up-regulated genes and 101 down-regulated genes, were identified. Enrichment analyses showed that the genes of the major module were largely associated with the cell cycle. All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples. This study identified a number of genes that may play important roles in the association of T2DM and HCC, including four genes which may be the target of metformin treatment for diabetes and HCC. The specific mechanisms involved remain to be identified.


Effect of LED therapy for the treatment nipple fissures: Study protocol for a randomized controlled trial.
Poor positioning of the child in relation to the breast and improper suckling are the main causes of nipple fissure. Treatment options for nipple fissures include drug therapy with antifungal and antibiotics, topical applications of lanolin, glycerin gel, creams and lotions, the milk itself, hot compresses, and silicone nipple shields. Studies involving light-emitting diode (LED) therapy have demonstrated anti-inflammatory properties, the enhancement of the wound repair process, and the control of pain. As it does not cause discomfort, is relatively inexpensive and may impede the discontinuation of breastfeeding, phototherapy could be a viable option for the treatment of nipple fissures. The principal objective of the proposed study is to evaluate the effectiveness of LED therapy for the treatment of nipple fissures in postpartum mothers. One hundred patients treated with a medical diagnosis of bilateral nipple trauma classified as nipple fissures or cracks will participate in the study, randomized into 2 groups: The control group will receive orientation regarding breast care and adequate breastfeeding techniques. The experimental group will receive the same orientation and phototherapy sessions using a device developed especially for the treatment of nipple trauma. Both groups will be followed up for 6 consecutive weeks.


[Fibromyalgia classification: are there different classes of patients?].
Fibromyalgia (FM) is one of the most frequent diseases causing chronic pain. Due to the heterogeneity of its clinical expression and the lack of standardized instruments to classify the signs and symptoms, the availability of a classification system would allow more homogeneous groups of patients to be identified and would permit individualizing diagnostic and therapeutic management. Correct classification of patients with FM requires individual diagnostic evaluation by a multidisciplinary team comprising the family doctor, a specialist in rheumatology or autoimmune diseases, a trauma doctor and a psychologist/psychiatrist. The diagnostic contribution of each specialist together with analysis of the timeline of appearance of signs and symptoms is essential in order to decide to which FM subgroup the patient belongs.


Integrated environmental evaluation of heavy metals and metalloids bioaccumulation in invertebrates and seaweeds from different marine coastal areas of sardinia, mediterranean sea.
In this work, three gastropods Patella vulgata, Osilinus turbinata, and Tahis clavigera, one echinoderm Parancetrotus lividus, one coelenterate Anemonia sulcata, and two seaweed Padina pavonica, and Cystoseira mediterranea were collected from three different marine areas of Sardinia in the Mediterranean sea and studied for heavy metals and metalloid content and accumulation trends. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used for the determination of Al, AS, B, Ba, Be, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Se, Sn, Sr, Te, Ti, V and Zn in the selected samples. The results showed that gastropods were capable of accumulating Al, Ba, Cu, Fe, Sr, and Zn; seaweeds can better concentrate Al, Fe, and Zn than all other species. At the same time, echinoderms and coelenterate had limited ability to store specific metals, showing a much more homogeneous distribution. PCA analysis allowed us to discriminate among the sites and the species. Cala Zafferano was the area with the higher values of accumulation of all metals in all species as expected, considering its proximity to industrial sites. The results of the analysis showed clearly that heavy metal and metalloid accumulation was different for each species studied. Therefore, for a correct environmental assessment of a given area, a comprehensive approach is strongly recommended by exploiting the different properties of both accumulation and concentration of the metals by different aquatic species.


Developing, evaluating and maintaining a standardized stormwater BMP effectiveness database.
The Urban Water Resources Research Council of the American Society of Civil Engineers, under a cooperative agreement with the US Environmental Protection Agency, released Version 1.0 of the National Stormwater Best Management Practices (BMP) Database to the stormwater management community in 1999. The product included a loaded database of 71 BMPs, as well as data entry software for standardized reporting of BMP test data. In conjunction with the database, the project team developed BMP performance evaluation protocols and applied them to the data contained in the initial database. Since the initial database release, 42 new BMP data sets have been added to the database, which is now accessible via the Internet at www.bmpdatabase.org along with associated data evaluation reports and other project documentation. A national stormwater BMP data clearinghouse continues to screen and post new BMP data to the database, as well as respond to inquiries from the public. An overview of both of the database software and results of the data evaluation are provided in this paper.


Guttate psoriasis following Ecstasy ingestion.
A 23-year-old man presented with the onset of a widespread pruritic eruption 4 days after ingestion of an Ecstasy tablet for the first time. The rash was characterized by small papules up to 10 mm in diameter distributed in a guttate pattern over most of his body and displaying the Köbner phenomena. Histology diagnosed a psoriasiform drug eruption. The eruption was not responsive to the initial treatment of topical betamethasone dipropionate 0.1% ointment and oral prednisolone. Prompt resolution was achieved with narrowband UVB treatment and avoidance of rechallenge.


Current status of antitumor therapy with monoclonal antibodies.
The potential power of monoclonal antibodies arises from their ability to recognize single antigenic determinants in a complex mixture of molecules or cells. The possibilities for cancer therapy are apparent. But to what extent has the potential been realized? What problems have arisen in clinical trials?


[Summary of tools for assessment of public health emergency response capability].
With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.


Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation.
Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro-/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin.


[The cause of complications of abdominal incision healing after cesarean section in cattle].
Based on a case analysis of patients with caesarean section (n = 252) performed at the Clinic for Obstetrics and Gynaecology in Cattle of the Veterinary School of Hannover, it was the aim of the following study to make a contribution to the aetiology of wound complications following caesarean section. Wound complications were classified as mild, moderate or severe according to the following criteria: mild: slight swelling in the area of the wound (wound edema or slight phlegmon), especially in the ventral corner; healing without therapy (n = 17 [6.7%]), moderate: seroma and moderate phlegmon; wound healing after conservative treatment with hyperemizing ointments (n = 16 [6.3%]), severe: secondary wound healing after lancing of the abscess, rinsing with acridine colour solution and hydrogen peroxide solution plus drainage with iodoform gauze (n = 23 [9.1%]). The following factors had a significant effect on the healing process: duration of parturition (18% and 37.7% wound complications in animal with normal and prolonged labor, respectively); macroscopic condition of the allantoic and/or amniotic fluid (19.7% and 47.8% wound complications in animals with normal and pathologic allantoic and/or amniotic fluid; respectively); degree of the exposure of the uterus outside the laparotomy wound (13.4% and 51.7% wound complications in cases with complete exposure of the uterus [i.e. complete exposure of the pregnant horn with one limb of the fetus, e.g. in anterior position, from hock joint to the claws] and incomplete or no exposure of the uterus, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Elder abuse risk factors: Perceptions among older Chinese, Korean, Punjabi, and Tamil immigrants in Toronto.
Elder abuse is a significant concern worldwide. Several factors are reported to increase the risk for elder abuse, but little is known about which factors are most relevant to immigrant communities. This study explored perceptions of risk factors for elder abuse among older immigrants, which is the first step toward designing effective interventions. This cross-sectional quantitative study was conducted between 2017 and 2019 in the Greater Toronto Area, Ontario, Canada and involved a convenience sample (N = 173) of older women and men from Chinese, Korean, Punjabi, and Tamil immigrant communities. Participants completed a questionnaire about the frequency and importance of risk factors of elder abuse in their respective community. Descriptive statistics were used to analyze the data within each immigrant community and analysis of variance to compare the factor ratings across communities. The immigrant communities differed (p < .05) in their perception of the risk factors. Factors rated as frequent and important (x̅ > 2.0 - midpoint of the rating scale) were social isolation, financial dependence, and lack of knowledge of English for Korean; financial dependence, physical dependence, and emotional dependence for Chinese; lack of knowledge of English, emotional dependence, and physical dependence for Tamil; and social isolation for Punjabi. The findings highlight the need for collaboration among public health and social services to work with immigrant communities in co-designing interventions to address these key risk factors and thereby reduce the risk of elder abuse.


Metagenomic and metabolic analyses of poly-extreme microbiome from an active crater volcano lake.
El Chichón volcano is one of the most active volcanoes in Mexico. Previous studies have described its poly-extreme conditions and its bacterial composition, although the functional features of the complete microbiome have not been characterized yet. By using metabarcoding analysis, metagenomics, metabolomics and enzymology techniques, the microbiome of the crater lake was characterized in this study. New information is provided on the taxonomic and functional diversity of the representative Archaea phyla, Crenarchaeota and Euryarchaeota, as well as those that are representative of Bacteria, Thermotogales and Aquificae. With culture of microbial consortia and with the genetic information collected from the natural environment sampling, metabolic interactions were identified between prokaryotes, which can withstand multiple extreme conditions. The existence of a close relationship between the biogeochemical cycles of carbon and sulfur in an active volcano has been proposed, while the relationship in the energy metabolism of thermoacidophilic bacteria and archaea in this multi-extreme environment was biochemically revealed for the first time. These findings contribute towards understanding microbial metabolism under extreme conditions, and provide potential knowledge pertaining to "microbial dark matter", which can be applied to biotechnological processes and evolutionary studies.


Genomic organization of the interleukin-1 locus.
Recent additions have expanded the interleukin (IL)-1 gene family to 10 members. We have determined the order, orientation, and intergenic distance of the nine IL-1 family genes that lie on human chromosome 2. We report cDNA sequences for the mouse orthologs of three of these genes. The order and orientation of the mouse genes have been mapped, and the mouse locus compared with the human locus. There is a break in the mouse locus of > 100 kb, compared with the human locus, located between Il1b and the most centromere-proximal of the novel mouse genes. The mouse seems to be missing an ortholog of human IL1F7.


High-content, cell-by-cell assessment of HER2 overexpression and amplification: a tool for intratumoral heterogeneity detection in breast cancer.
Immunohistochemistry and fluorescence in situ hybridization are the two standard methods for human epidermal growth factor receptor 2 (HER2) assessment. However, they have severe limitations to assess quantitatively intratumoral heterogeneity (ITH) when multiple subclones of tumor cells co-exist. We develop here a high-content, quantitative analysis of breast cancer tissues based on microfluidic experimentation and image processing, to characterize both HER2 protein overexpression and HER2 gene amplification at the cellular level. The technique consists of performing sequential steps on the same tissue slide: an immunofluorescence (IF) assay using a microfluidic protocol, an elution step for removing the IF staining agents, a standard FISH staining protocol, followed by automated quantitative cell-by-cell image processing. Moreover, ITH is accurately detected in both cluster and mosaic form using an analysis of spatial association and a mathematical model that allows discriminating true heterogeneity from artifacts due to the use of thin tissue sections. This study paves the way to evaluate ITH with high accuracy and content while requiring standard staining methods.


Olfactory Function and Depression: A Meta-Analysis.
We investigated the relationship between olfactory function and depression and suggested future research in this area from rhinology. We independently searched 5 databases (PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database) for recent studies published from December 2019 to the present. From the obtained studies, we reviewed the findings on olfactory function and depression using a questionnaire to measure depression and olfactory tests. The olfactory function test score based on the UPSIT-40 (standardized mean difference = -.37 [-.66; -.08], P = .0123) was significantly lower in the depression group than in the control group. The olfactory function score based on the Sniffin' sticks test for identification, discrimination, and threshold was lower in the depression group than in the control. A meta-analysis of the studies showed that depressed patients showed lower olfactory function than the control group. The findings revealed that an understanding of the relationship between olfaction and depression can be determined using an analysis methodology and a standardized olfactory test. Olfactory functioning and processing are highly integrated with emotion and memory through projections from the olfactory bulb to the central areas.


A systematic review and meta-analysis of complications following the posterior and lateral surgical approaches to total hip arthroplasty.
Total hip arthroplasty is one of the most commonly performed orthopaedic procedures. Despite this, medical evidence to inform the choice of surgical approach is lacking. Currently in the UK, the two most frequently performed approaches to the hip are the posterior and the direct lateral. This systematic review was performed according to Cochrane guidelines following an extensive search for prospective controlled trials published in any language before January 2014. Of the 728 records identified from searches, 6 prospective studies (including 3 randomised controlled trials) involving 517 participants provided data towards this review. Compared with the lateral approach, the posterior approach conferred a significant reduction in the risk of Trendelenburg gait (odds ratio [OR]: 0.31, p=0.0002) and stem malposition (OR: 0.24, p=0.02), and a non-significant reduction in dislocation (OR: 0.37, p=0.16) and heterotopic ossification (OR: 0.41, p=0.13). Neither approach conferred a functional advantage. We draw attention to the paucity of evidence and the need for a further randomised trial.


[Integration of psychiatric treatment and rehabilitation].
Residual symptoms exist in psychiatric disorders, especially in schizophrenia. These become more serious according to the length of stay in hospital. Therefore, rehabilitation programs are necessary throughout the hospitalization. In the acute state also, psycho-social therapy and education are important. The most important is to give them the motivation toward their post-hospital life. Short stay in their residence before discharge gives us the information about the problems of patients' community lives. And to the patients and their families, it gives the confidence of community-living. 'Home-visit' by nursing staffs during this short stay further shows us how to support them and their families. These rehabilitation and support programs being prepared since 1986, the hospital-beds decreased from 603 to 505, admitted patients increased from 444 to 1586, and average length of stay shortened from 473 to 108 days. Whereas being treated outpatients increased from 2010 to 3439 for 10 years after 1990.


Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells.
Mutational activation of BRAF is a frequent event in human malignant melanomas suggesting that BRAF-dependent signaling is conducive to melanoma cell growth and survival. Previously published work reported that melanoma cells exhibit constitutive anti-apoptotic nuclear factor kappaB (NF-kappaB) transcription factor activation triggered by proteolysis of its inhibitor IkappaB. IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase. Here, we report that melanocytes expressing a conditionally oncogenic form of BRAF(V600E) exhibit enhanced beta-Trcp expression, increased IKK activity and a concomitant increase in the rate of IkappaBalpha degradation. Conversely, inhibition of BRAF signaling using either a broad-spectrum Raf inhibitor (BAY 43-9006) or by selective knock-down of BRAF(V600E) expression by RNA interference in human melanoma cells leads to decreased IKK activity and beta-Trcp expression, stabilization of IkappaB, inhibition of NF-kappaB transcriptional activity and sensitization of these cells to apoptosis. Taken together, these data support a model in which mutational activation of BRAF in human melanomas contributes to constitutive induction of NF-kappaB activity and to increased survival of melanoma cells.


Body composition in Aboriginal Australians.
The anthropomorphic features of Australian Aborigines have been described, measured and reported in considerable detail by explorers, anthropologists, anatomists and medical practitioners. These reports have provided evidence that some aspects of Aboriginal physique differ considerably from those of Europeans. For example, it has been reported that Australian Aborigines of both sexes have relatively shorter trunks and longer legs than almost every other ethnic group, that body proportions differ less between males and females, and that traditionally Australian Aborigines had a lower weight for stature than Europeans of the same age and sex. Less information exists on their body composition. Available data, however, indicate that there may also be differences in body fat distribution, but not in the amount of fat-free mass (FFM) per unit of stature, between Australian Aborigines and Australians of European origin An analysis of the available data on body composition suggests that the very low body mass index (BMI) values observed in apparently healthy Aborigines, and the different relationship in this ethnic group between BMI and the amount of subcutaneous fat, are more likely to be due to a more central body fat distribution than to differences in skeletal body proportions between Australian Aborigines and Australians of European origin.


Identification of the promoters directing in vivo expression of hemolysin genes in Proteus vulgaris and Escherichia coli.
The hemolytic activity of Escherichia coli and Proteus vulgaris is determined by common contiguous genes encoding synthesis (hly C, hly A) and specific secretion (hly B, hly D) of active hemolysin. Nevertheless, the hly C-proximal DNA sequences directing production of the homologous hemolysins by the recombinant DNAs P. vulgaris pVU763-709 and E. coli pANN202-312 showed no extensive homology. Primer extension and S1 nuclease protection were used to define in the two sequences the 5' termini of hly transcripts synthesized in vivo and thus to infer the active hly promoters sequences. The E. coli hly C upstream region contained three separate promotors directing in vivo hly transcription, while the corresponding transcription of the P. vulgaris hly operon originated from a single distinct promotor, the -35 and -10 sequences of which formed part of an inverted repeat sequence. Elevated hemolytic activity caused by upstream Tn5 insertions in pVU763-709 resulted from increased transcription from this promotor.


Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus.
Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.


Implications of European corn borer, Ostrinia nubilalis, infestation in an Aspergillus flavus-biocontrolled corn agroecosystem.
A novel biocontrol strategy consisting of field application of bioplastic-based granules inoculated with a non-toxigenic Aspergillus flavus L. strain has recently been shown to be effective for reducing aflatoxin contamination in corn. This study focused on other factors that may affect the feasibility of this biocontrol technique, and more specifically the role of the European corn borer (ECB), Ostrinia nubilalis H., in the dispersal and infestation of A. flavus in corn and its impact on crop yield. In spite of the high percentage of corn ears showing larval feeding damage, ECB-bored kernels accounted for only 3 and 4% in 2009 and 2010 respectively. Most of the damaged kernels were localised in the ear tip or immediately below. More precisely, the average incidence of ECB-bored kernels in the upper end of the ear was 32%. However, less than 5% of kernels from the central body of the ear, which includes the majority of kernels, were injured by ECB. Although ECB larvae showed a high tolerance to aflatoxin B1 and thus had the potential to serve as vectors of the mould, fungal infection of kernels was poorly associated with insect damage. ECB infestation resulted in grain yield losses not exceeding 2.5%.


Low-temperature synthesis of single-walled carbon nanotubes by alcohol gas source growth in high vacuum.
Carbon nanotube (CNT) growth was carried out on SiO2/Si substrates with a Co catalyst using an alcohol gas source method in an ultra-high vacuum chamber. The resulting CNTs were characterized by scanning electron microscopy (SEM), Raman spectroscopy and transmission electron microscopy (TEM). Reducing the ethanol pressure decreased the optimum growth temperature for maximum yield, enabling single-walled carbon nanotube (SWNT) growth at 400 degrees C. By employing an Al2Ox buffer layer, SWNT yield increased several times, even at 400 degrees C. Under TEM observation, the Co particle size on the Al2Ox layers did not show a significant dependence on the growth temperature between 400 and 700 degrees C. Raman and TEM results confirmed activation of Co particles with larger diameter (>1 nm) by the Al2Ox buffer layer.


Chiral separation of aliphatic primary amino alcohols as o-phthaldialdehyde/mercaptoethanol derivatives on polysaccharide-based chiral stationary phases.
A sensitive chiral high performance liquid chromatography (HPLC) method for the determination of aliphatic primary amino alcohol isomers with o-phthaldialdehyde/mercaptoethanol precolumn derivatization has been developed and validated. Seven chiral columns were tested in a reversed phase mode. Excellent enantioseparation with the resolution more than 2.0 was achieved on Chiralcel OJ-3R. The effect of various chromatographic conditions including column temperature, acetonitrile content in the mobile phase, buffer pH, buffer concentration, and buffer type in the mobile phase on the retention and the selectivity was investigated. The final mobile phase consisted of binary mixture of 20mM ammonium formate solution with acetonitrile (75:25; v/v). The analyses were performed at mobile phase flow rate of 1.0 mL/min and the column temperature of 40°C. The fluorescence detection was performed at excitation wavelength of 345 nm and emission wavelength of 450 nm. The developed method was fully validated in terms of linearity, sensitivity, accuracy, precision, intermediate precision, and selectivity according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines using internal normalization procedure. The proposed chiral method was proved to be highly sensitive, simple, and rapid and was successfully applied to the determination of D-Valinol content in commercially available samples of L-Valinol.


[Effects of moxibustion at different time points on foot swelling, serum level of TNF-α and circadian rhythm in rats with rheumatoid arthritis].
To study the effects of moxibustion at different time points on serum level of tumor necrosis factor-α (TNF-α) in rats with rheumatoid arthritis (RA), and to explore its regulation mechanism on circadian rhythm. A total of 96 Sprague-Dawley (SD) adult rats were randomly assigned into a blank group, a model group, a moxibustion at 5-7 AM group and a moxibustion at 5-7 PM group, 24 rats in each group, half male and half female. Each group was further divided into a 0 AM group, a 6 AM group, a 12 N group and a 6 PM group, 6 rats in each group. All rats were treated with the 12 h/12 h light-dark cycle in the whole process of experiment. Except for the blank group, all rats were treated with intracutaneous injection of freund's complete adjuvant (FCA) at right foot pad to establish the RA model. The rats at the two moxibustion groups were treated with grain-sized moxibustion at "Shenshu" (BL 23) and "Zusanli" (ST 36) at 5-7 AM and 5-7 PM, respectively, one side per treatment, once a day; six treatments were taken as one course and 3 courses were given with an interval of one day between courses. The rats in the remaining groups were treated with identical fixation but without moxibustion intervention. The right foot volume was measured before model establishment, after model establishment and after treatment. The blood samples were collected after treatment and the serum level of TNF-α was measured by ELISA. The SPSS 21.0 software and Halberg Cosinor were adopted to analyze the experiment data. After treatment, compared with the blank group, the foot swelling severity was significantly increased in the model group, moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (all P<0.01); compared with the model group, the foot swelling severity was significantly reduced in the moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (both P<0.01). Compared with the blank group, the serum level of TNF-α was increased significantly in the model group and moxibustion at 5-7 AM group (both P<0.05); compared with the model group, the serum level of TNF-α was reduced significantly in the moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (both P<0.05). The serum level of TNF-α showed circadian rhythm in all the groups (all P<0.05), and the peak appeared at night phase; compared with the blank group, the median value of TNF-α was increased significantly in the model group (P<0.05), the peak phase was delayed and the amplitude was increased (P<0.05); compared with the model group, the median value of TNF-α was significantly reduced in the moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (P<0.01), the peak phase was advanced and the amplitude was reduced (P<0.05). Moxibustion could effectively reduce the serum level of TNF-α to relieve the foot swelling severity in RA rats. Moxibustion could regulate the circadian rhythm of TNF-α to play its effects on the inhibition of the synthesis of TNF-α. No efficacy is observed between the treatment at 5-7 AM and 5-7 PM.


Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3‑derived sphere-forming cells.
Casein kinase 2 (CK2) is a protein kinase which is frequently activated in cancer. The Hedgehog (Hh) signaling pathway is involved in the stimulation of cancer stem cell growth. Its aberrant activation has been validated in several types of cancer, including ovarian cancer. In the present study, the sphere‑forming cells (SFCs) of the human ovarian cancer SKOV3 cell line were observed to have self‑renewal capacity, indicating the possession of ovarian cancer stem‑like cell properties. SKOV3‑derived SFCs had higher levels of CK2α and glioma‑associated oncogene 1 (Gli1) proteins compared with those of parental cells. Apigenin, a common flavonoid, significantly inhibited the self‑renewal capacity and the protein expression of CK2α and Gli1 proteins in the SKOV3‑derived SFCs, which occurred in a concentration‑dependent manner. In addition, CK2α small interfering RNA downregulated the protein expression of CK2α and Gli1 and synergistically inhibited the self‑renewal capacity of the SKOV3‑derived SFCs with apigenin. However, forced overexpression of CK2α resulted in an increase in the expression of CK2α and Gli1 and attenuated the apigenin‑inhibited self‑renewal effect in the SKOV3‑derived SFCs. These results suggested that apigenin inhibited the self‑renewal capacity of SKOV3‑derived SFCs and was involved in downregulating the expression of Gli1 by the inhibition of CK2α.


Butein, a specific protein tyrosine kinase inhibitor.
Butein, a plant polyphenol, was shown to be a specific protein tyrosine kinase inhibitor. This compound inhibited not only the epidermal growth factor (EGF)-stimulated auto-phosphotyrosine level of EGF receptor in HepG2 cells but also tyrosine-specific protein kinase activities of EGF receptor (IC50 = 65 microM) and p60c-src (IC50 = 65 microM) in vitro. The inhibition was competitive to ATP and non-competitive to the phosphate acceptor, poly (Glu, Ala, Tyr) 6:3:1 for EGF receptor tyrosine kinase. In contrast, butein non-significantly inhibited the activities of serine- and threonine-specific protein kinases, such as protein kinase C (PKC) and cAMP-dependent protein kinase (PKA).


Antischistosomal Activity of Origanum majorana, Ziziphus spina-christi, and Salvia fruticosa Plant Extracts on Hamster Infected with Schistosoma haematobium.
World Health Organization (WHO) has approved only one treatment for schistosomiasis, praziquantel (PZQ), but some poor efficacy was noticed in patients during the early stage of infection. Therefore, researchers have intensified their efforts to research new alternative medicines to treat schistosomiasis. In the present study, in vitro as well as in vivo studies have been accomplished to evaluate the effect of Origanum majorana, Ziziphus spina-christi, and Salvia fruticosa extracts in a different concentration 500, 250, 125, 62.5, and 31.25 μg/ml on golden hamster infected by Egyptian strains of schistosome (Schistosoma haematobium). In vitro, the adult worms and schistosomula of S. haematobium were investigated in RPMI-1640 medium for 48 hrs. The results showed that the concentration 500, 250, and 125 μg/ml of Origanum majorana, and Ziziphus spina-christi caused dead of 100% of Egyptian Schistosoma strains of adult worm and schistosomula of S. haematobium within 6 to 12 hrs of incubation. On the other hand, the extract of Salvia fruticosa at concentrations 500, 250, and 125 μg/ml showed death 100% parasites after 12 to 24 hrs of incubation. Inclusion, Origanum majorana, and Ziziphus spina-christi showed effectiveness against Egyptian Schistosoma strains (S. haematobium), a slight decrease in Salvia fruticosa was observed. Therefore, these medical plant extracts may be used as a safe and effective treatment for schistosomiasis.


Biosynthesis of chondroitin sulfate. Purification of glucuronosyl transferase II and use of photoaffinity labeling for characterization of the enzyme as an 80-kDa protein.
A photoaffinity analogue, [beta-32P]5-azido-UDP-GlcA, was used to photolabel the enzymes that utilize UDP-GlcA in cartilage microsomes and rat liver microsomes. SDS-polyacrylamide gel electrophoresis analysis of photolabeled cartilage microsomes, which are specialized in chondroitin sulfate synthesis, showed a major radiolabeled band at 80 kDa and other minor radiolabeled bands near 40 and 60 kDa. Rat liver microsomes, which are enriched for enzymes of detoxification by glucuronidation, had a different pattern with multiple major labeled bands near 50-60 and 35 kDa. To determine that the photolabeled 80-kDa protein is the GlcA transferase II, we have purified the enzyme from cartilage microsomes. This membrane-bound enzyme, involved in the transfer of GlcA residues to non-reducing terminal GalNAc residues of the chondroitin polymer, has now been solubilized, stabilized, and then purified greater than 1350-fold by sequential chromatography on Q-Sepharose, heparin-Sepharose, and WGA-agarose. The purified enzyme exhibited a conspicuous silver-stained protein band on SDS-polyacrylamide gel electrophoresis that coincided with the major radiolabeled band of 80 kDa. SDS-polyacrylamide gel analysis of photoaffinity-labeled active fractions from the Q-Sepharose, heparin-Sepharose, and WGA-agarose also indicated only the single radiolabeled band at 80 kDa. Intensity of photolabeling in each of the fractions examined coincided with enzyme activity. The photolabeling of this 80-kDa protein was saturable with the photoprobe and could be inhibited by the addition of UDP-GlcA prior to the addition of the photoprobe. Thus, the photolabeling with [beta-32P]5-azido-UDP-GlcA has identified the GlcA transferase II as an 80-kDa protein. The purified enzyme was capable of transferring good amounts of GlcA residues to chondroitin-derived pentasaccharide with negligible transfer to pentasaccharides derived from hyaluronan or heparan.


Density measurement of shock compressed foam using two-dimensional x-ray radiography.
We have used spherically bent quartz crystal to image a laser-generated shock in a foam medium. The foam targets had a density of 0.16 g/cm(3) and thickness of 150 microm, an aluminum/copper pusher drove the shock. The experiment was performed at the Titan facility at Lawrence Livermore National Laboratory using a 2 ns, 250 J laser pulse to compress the foam target, and a short pulse (10 ps, 350 J) to generate a bright Ti K alpha x-ray source at 4.5 keV to radiograph the shocked target. The crystal used gives a high resolution (approximately 20 microm) monochromatic image of the shock compressed foam.


Barrier membranes: More than the barrier effect?
To review the knowledge on the mechanisms controlling membrane-host interactions in guided bone regeneration (GBR) and investigate the possible role of GBR membranes as bioactive compartments in addition to their established role as barriers. A narrative review was utilized based on in vitro, in vivo and available clinical studies on the cellular and molecular mechanisms underlying GBR and the possible bioactive role of membranes. Emerging data demonstrate that the membrane contributes bioactively to the regeneration of underlying defects. The cellular and molecular activities in the membrane are intimately linked to the promoted bone regeneration in the underlying defect. Along with the native bioactivity of GBR membranes, incorporating growth factors and cells in membranes or with graft materials may augment the regenerative processes in underlying defects. In parallel with its barrier function, the membrane plays an active role in hosting and modulating the molecular activities of the membrane-associated cells during GBR. The biological events in the membrane are linked to the bone regenerative and remodelling processes in the underlying defect. Furthermore, the bone-promoting environments in the two compartments can likely be boosted by strategies targeting both material aspects of the membrane and host tissue responses.


A randomized controlled trial of cyanoacrylate versus alcohol injection in patients with isolated fundic varices.
Treatment of bleeding gastric varices (GVs) is still controversial, mainly because of anecdotal studies or inclusion of patients with GVs located at different sites that have variable incidences of bleeding. A prospective study was undertaken to compare the efficacy and safety of GV sclerotherapy using alcohol and GV obturation using cyanoacrylate glue. Thirty-seven consecutive patients with portal hypertension and endoscopic evidence of isolated GVs, 17 presenting with histories of active bleeding, were randomized to receive endoscopic intervention either with alcohol (n = 17) or with cyanoacrylate glue (n = 20) injection. Variceal obliteration, rebleeding, or death was the endpoint. The glue was significantly more effective in achieving variceal obliteration than alcohol (100% vs 44%, p < 0.05). Furthermore, this could be achieved in a significantly shorter period (2.0 +/- 1.6 vs 4.7 +/- 3.2 wk, p < 0.05) and with a smaller volume of the agent. Cyanoacrylate glue injection could achieve arrest of acute GV bleeding more often than alcohol (89% vs 62%), and the need for rescue surgery was less; the difference was, however, not significant. Six patients died from uncontrolled GV bleeding, four being in the alcohol group. During a mean follow-up of 15.4 +/- 3.7 months there was no recurrence of GVs in either group. Our results show that cyanoacrylate is more effective and achieves GV obliteration faster than injection sclerotherapy with alcohol. It also appears to be more useful in controlling acute GV bleeding, with less of a need for rescue surgery.


[An immunohistochemical investigation of estrogen receptor in human breast cancer].
An immunohistochemical investigation of 62 human breast Cancers has been conducted using two different monoclonal antibodies, ER-ICA and ER-D 5, for the demonstration of the estrogen receptor. ER-ICA was found to be positive in 28 cases (45.9%) whereas ER-D 5 was positive in 41 cases (68.3%). In 34 cases, the results were compared to results of a biochemical assay that employed dextran-coated charcoal. The overall concordance between the ER-ICA and the DCC was 78.8%, whereas ER-D 5 and DCC was 60.6%. We thus have concluded that ER-ICA is the more sensitive antibody for evaluating the estrogen receptor status in human breast cancer cases by this immunohistochemical analysis.


Recent Understandings Toward Coronavirus Disease 2019 (COVID-19): From Bench to Bedside.
In late December 2019, an unprecedented outbreak of coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2) (previously named 2019-nCoV) in Wuhan became the most challenging health emergency. Since its rapid spread in China and many other countries, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern (PHEIC) on 30th January 2020 and a pandemic on 11th March 2020. Thousands of people have died, and there are currently no vaccines or specific antiviral drugs for COVID-19. Therefore, it is critical to have a comprehensive understanding of the virus. In this review, we highlight the etiology, epidemiology, pathogenesis and pathology, clinical characteristics, diagnosis, clinical management, prognosis, infection control and prevention of COVID-19 based on recent studies.


CO adsorption and desorption on size-selected Pd(n)/TiO2(110) model catalysts: size dependence of binding sites and energies, and support-mediated adsorption.
The nature of CO adsorption on Pd(n)/TiO(2)(110) (n = 1, 2, 7, 20) has been examined using temperature-programmed desorption (TPD), temperature-dependent helium ion scattering (TD-ISS), and X-ray photoelectron spectroscopy (XPS). All samples contain the same number of Pd atoms (0.10 ML-equivalent) deposited as different size clusters. The TPD and TD-ISS show that CO binds in two types of sites associated with the Pd clusters. The most stable sites are on top of the Pd clusters ("on-top" sites), however, there are also less stable sites, in which CO is bound in association with, but not on top of the Pd ("peripheral" sites). For saturation CO coverage over a fixed atomic concentration of Pd (present in the form of Pd(n) clusters of varying size), the population of CO in peripheral sites decreases with increasing cluster size, while the on-top site population is size-independent. This is consistent with what geometric considerations would predict for the density of the two types of sites, provided the clusters adsorb predominantly as 2D islands, which ISS results suggest to be the case. The XPS analysis indicates that CO-Pd binding is dominated by π-backbonding to the Pd(n) clusters. The results also show evidence for efficient support-mediated adsorption (reverse-spillover) of CO initially impinging on TiO(2) to binding sites associated with the Pd clusters.


In silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem-Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation.
Donor T-cell mediated graft versus host (GVH) effects may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the human leukocyte antigen (HLA) molecules in each donor-recipient pair undergoing stem-cell transplantation (SCT). Whole exome sequencing has previously demonstrated a large number of non-synonymous single nucleotide polymorphisms (SNP) present in HLA-matched recipients of SCT donors (GVH direction). The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric peptides incorporating the variant amino acid resulting from these SNPs were interrogated in silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM) and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data were interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting a HLA-specific alloreactivity potential.


Arginine-Rich Peptidomimetic Ampicillin/Gentamicin Conjugate To Tackle Nosocomial Biofilms: A Promising Strategy To Repurpose First-Line Antibiotics.
Combined therapy with penicillins and aminoglycosides has been proved beneficial to address many persistent bacterial infections with possible synergistic effects. However, the different pharmacokinetic profiles of these two antibiotic classes may not guarantee a concerted spatio-temporal delivery at the site of action, decreasing the efficacy of this combination and promoting resistance. Herein, we propose a multifunctional antibiotic-polymer conjugate, designed to colocalize ampicillin and gentamicin to tackle persistent biofilm infections. The two antibacterial molecules were grafted along with the amino acid l-arginine to a biocompatible polymer backbone with peptidomimetic hydrophilic structure, obtaining the antimicrobial poly(argilylaspartamide-co-aspartic) acid-ampicillin, gentamicin (PAA-AG) conjugate. The PAA-AG conjugate displayed excellent biocompatibility on human cell lines if compared with free drugs, potentially enlarging their therapeutic window and safety, and suitable mucoadhesive characteristics which may help local treatments of mucosal infections. Studies on planktonic cultures of clinical and reference strains of S. aureus, P. aeruginosa, and E. coli revealed that PAA-AG holds a broad-spectrum antibacterial efficacy, revealing high potency in inhibiting the growth of the tested strains. More interestingly, PAA-AG exhibited excellent antibiofilm activity on both Gram+ and Gram- communities, showing inhibition of their formation at subMIC concentrations as well as inducing the regression of mature biofilms. Given the high biocompatibility and broad antibiofilm efficacy, combined with the opportunity for synchronous co-delivery, the PAA-AG conjugate could be a valuable tool to increase the success of ampicillin/gentamicin-based antibiotic multitherapy.


A toy model mimicking cage effect, structural fluctuations, and kinetic constraints in supercooled liquids.
In this work, we implement new toy models coined to reproduce the cage effect with variants including structural fluctuations and different kinetic constraints. We introduce structural fluctuations in the models from a distribution of the cages opening probabilities and a kinetic constraint from a variation of that probability with the local number of molecules involved in the creation of the cage. We model separately the caging mean field experienced by each molecule, and the cooperative mechanism with the kinetic constraint condition. We find that strong dynamic heterogeneities are present in the models with kinetic constraints. We find that the heterogeneities do not depend on the cage escaping probabilities, while the heterogeneities increase sharply with the strengthening of the kinetic constraint conditions.


The Advent of Biomolecular Ultrasound Imaging.
Ultrasound imaging is one of the most widely used modalities in clinical practice, revealing human prenatal development but also arterial function in the adult brain. Ultrasound waves travel deep within soft biological tissues and provide information about the motion and mechanical properties of internal organs. A drawback of ultrasound imaging is its limited ability to detect molecular targets due to a lack of cell-type specific acoustic contrast. To date, this limitation has been addressed by targeting synthetic ultrasound contrast agents to molecular targets. This molecular ultrasound imaging approach has proved to be successful but is restricted to the vascular space. Here, we introduce the nascent field of biomolecular ultrasound imaging, a molecular imaging approach that relies on genetically encoded acoustic biomolecules to interface ultrasound waves with cellular processes. We review ultrasound imaging applications bridging wave physics and chemical engineering with potential for deep brain imaging.


Microencapsulation of tumor necrosis factor oligomers: a new approach to proinflammatory cytokine inhibition.
Antisense oligonucleotides offer great therapeutic potential provided adequate intracellular penetration can be achieved. In this study, we evaluated the effectiveness of microencapsulating antisense oligonucleotides to tumor necrosis factor (TNF) in suppressing TNF release in vitro and in vivo. Microencapsulation of TNF oligomers was performed using albumin to produce microcapsules 0.6-1.0 mum in size that target phagocytic cells. Albumin microcapsules containing fluoresceinated TNF oligomers were incubated with U-937 cells to observe uptake. Microcapsules were added to whole blood and stimulated with Escherichia coli endotoxin. Endotoxin was given intravenously (i.v.) to rats along with 100 mug microencapsulated TNF oligomers to determine TNF inhibition and animal survival. E. coli was given intraperitoneally (i.p.) along with gentamicin and microencapsulated TNF oligomers to assess TNF inhibition and animal survival. The duration of microencapsulated antisense TNF oligomers was also determined in vivo. The results demonstrated rapid uptake of the microcapsules by macrophages after 2 h and 4 h incubation. There was improvement in TNF inhibition in vitro and improved animal survival by microencapsulated antisense in both endotoxin (100% survival) and peritonitis models (70% survival) compared with free antisense oligomers in solution. Microencapsulation extended the duration of action of the oligomers to 72 h. Intracellular targeting of macrophages with antisense oligomers to TNF by microencapsules as a delivery system improves TNF inhibition using the models of whole blood endotoxin stimulation and endotoxic shock and peritonitis in rats.


Capturing nascent extracellular vesicles by metabolic glycan labeling-assisted microfluidics.
Extracellular vesicle (EV) secretion is a dynamic process crucial to cellular communication. Temporally sorting EVs, i.e., separating the newly-produced ones from the pre-existing, can allow not only deep understanding of EV dynamics, but also the discovery of potential EV biomarkers that are related to disease progression or responsible to drug intervention. However, the high similarity between the nascent and pre-existing EVs makes temporal separation extremely challenging. Here, by co-translational introduction of azido groups to act as a timestamp for click chemistry labelling, we develop a microfluidic-based strategy to enable selective isolation of nascent EVs stimulated by an external cue. In two mouse models of anti-PD-L1 immunotherapy, we demonstrate the strategy's feasibility and reveal the high positive correlation of nascent PD-L1+ EV level to tumor volume, suggesting an important role of nascent EVs in response to immunotherapy in cancer treatment.


Physicochemical, structural, and adsorption characteristics of DMSPS-co-DVB nanopolymers.
The aim of this work is the synthesis and characterization of the series of S,S'-thiodi-4,1-phenylene bis(thio-methacrylate)-co-divinylbenzene (DMSPS-co-DVB) nanomaterials. The series of new nanopolymers including three mixed systems with different ratios of DMSPS and DVB components, DMSPS-co-DVB = 1:1, DMSPS-co-DVB = 1:2, and DMSPS-co-DVB = 1:3, was synthesized in the polymerization reaction. The research task is to investigate the influence of the reaction mixture composition on morphological, textural, and structural properties of final nanosystems including size, shape, and agglomeration effect. The advanced biphasic nanomaterials enriched with thiol groups were successfully synthesized as potential sorbents for binding organic substances, heavy metals, or biomolecules. To determine the impact of the DMSPS monomer on the final properties of DMSPS-co-DVB nanocomposites, several techniques were applied to reveal the nano-dimensional structure (SAXS), texture (low-temperature nitrogen sorption), general morphology (SEM), acid-base properties (potentiometric titration), and surface chemistry and phase bonding effectiveness (FTIR/ATR spectroscopy). Finally, kinetic studies of aniline sorption on polymeric materials were performed.


Pulsed Microfluid Force-Based On-Chip Modular Fabrication for Liver Lobule-Like 3D Cellular Models.
In vitro three-dimensional (3D) cellular models with native tissue-like architectures and functions have potential as alternatives to human tissues in regenerative medicine and drug discovery. However, it is difficult to replicate liver constructs that mimic in vivo microenvironments using current approaches in tissue engineering because of the vessel-embedded 3D structure and complex cell distribution of the liver. This paper reports a pulsed microflow-based on-chip 3D assembly method to construct 3D liver lobule-like models that replicate the spatial structure and functions of the liver lobule. The heterogeneous cell-laden assembly units with hierarchical cell distribution are fabricated through multistep photopatterning of different cell-laden hydrogels. Through fluid force interaction by pulsed microflow, the hierarchical assembly units are driven to a stack, layer by layer, and thus spatially assemble into 3D cellular models in the closed liquid chamber of the assembly chip. The 3D models with liver lobule-like hexagonal morphology and radial cell distribution allow the dynamic perfusion culture to maintain high cell viability and functional expression during long-term culture in vitro. These results demonstrate that the fabricated 3D liver lobule-like models are promising for drug testing and the study of individual diagnoses and treatments.


The pathogenesis of rheumatoid arthritis: a guide to therapy.
The cause of rheumatoid arthritis (RA) is unknown; however, extensive research has yielded great insight into its pathogenesis. Lymphocytes play a significant role, but a lesser role in the perpetuation of late disease. The rheumatoid synovium is composed primarily of fibroblasts and monocytes that produce inflammatory cytokines, of which interleukin-1 and tumor necrosis factor are of key importance. Potential regulatory mechanisms balancing the effects of these cytokines are inadequate to prevent joint damage and subsequent disability. These cytokines seem responsible for stimulating destructive processes in the joint via induction of prostaglandins, angiogenesis, chemokines, adhesion molecules, osteoclastogenesis, and matrix metalloproteinases. This review discusses recent research findings in the immunopathogenesis of RA with respect to potential targets for therapy.


[PATHOMORPHOLOGICAL CHANGES UNDER LATENT MASTOIDITIS].
In our opinion it is caused by incomplete awareness of the distribution of pathological process and the character of morphological changes in the patients. In this regard, we studied structural changes in the soft and bone tissue taken from various cavities of the middle ear system. Operating material was formed in paraffin after the fixation and proper processing. We proceed with decalcification of bone tissues in 15-20% nitric acid. We painted 5-6 mm thick peels prepared on the rotating microtome with hematoxylin and eosin. The microscopic examination revealed inflammatory-destructive changes in the mucous membrane as well as in the bone tissues, also serous inflammation-fibrin inflammation, and well-expressed edema. The inflammatory infiltration demonstrated the presence of lymphocytes, macrophages, plasmocytes and also predominantly dislocated leukocytes. There were also revealed various amount of glandular structures. The bone tissues - along with the inflammatory infiltration - revealed destructive cells, which contained osteoclast, epithelial cells and fibroblasts. The mentioned structural changes should be assessed as demonstration of an osteitis and osteomyelitis. Based on the above mentioned, we believe that treatment of latent mastoiditis requires surgical method and it is necessary the complete sanitization of not only the granulating tissue but the damaged bone masses. Otherwise, the remaining inflammatory nidus may cause a relapse. The correct treatment of latent mastoiditis in turn will reduce the mortality rate and the percentage of disability.


Multiplexed digital holography for fluid surface profilometry.
Digital holography (DH) has been widely used for imaging and characterization of microstructures and nanostructures in materials science and biology and also has the potential to provide high-resolution, nondestructive measurement of fluid surfaces. DH setups capture the complex wavefronts of light scattered by an object or reflected from a surface, allowing the quantitative measurements of their shape and deformation. However, their use in fluid profilometry is scarce and has not been explored in much depth to the best of our knowledge. We present an alternative use for a DH setup that can measure and monitor the surface of fluid samples. Based on DH reflectometry, our modeling shows that multiple reflections from the sample and the reference interfere and generate multiple holograms of the sample, resulting in a multiplexed image of the wavefront. The individual interferograms can be isolated in the spatial frequency domain, and the fluid surface can be digitally reconstructed from them. We further show that this setup can be used to track changes in the surface of a fluid over time, such as during the formation and propagation of waves or the evaporation of surface layers.


Psychological assessment and AIDS research with intravenous drug users: challenges in measurement.
The instruments used for psychological assessment have been under close scrutiny for many years. In particular, ethnic and racial minorities have pointed out that misapplication of instruments standardized to White middle-class norms can result in incorrect assessments. An analogous situation exists with IVDUs. In the work of the present authors with IVDUs, they were found to be a very diverse group. Contrary to common wisdom, they differ by race, ethnicity, age, and drug use profiles. However, their economic circumstances and social stigma make them a special case in terms of psychological assessment. Given the unique characteristics of IVDUs, it behooves researchers to carefully examine the standardized instruments that are available for psychological evaluation. Too often, measures standardized on White middle-class samples lack the value neutrality that makes them applicable across disparate groups. In addition, many such measures are designed with certain presumptions that do not necessarily hold true with this population (e.g., willingness and/or ability to communicate intimate information about one's feelings and psychological states). This article briefly describes some of the challenges encountered in examining standardized instruments for use in the study of IVDUs, their health psychology and AIDS-related behavior. Concerns with self-report biases, literacy, attentional focus, measurement constructs, and drug states confounding psychological states all pose challenges to psychological research with this heterogeneous population. While the need for direct intervention on the sexual and needle-sharing behaviors of IVDUs remains paramount in the combat against the spread of AIDS, researchers must also continue with the further development of basic measurement tools.(ABSTRACT TRUNCATED AT 250 WORDS)


Apolipoprotein E4, amyloid, and cognition in Alzheimer's and Lewy body disease.
The role of apolipoprotein E4 (APOE4) in the risk of Alzheimer's disease (AD) and Lewy body disease (LBD), and their relationship with β-amyloid deposition and cognitive dysfunction, remain unclear. Using amyloid and dopamine transporter imaging, we enrolled 126 controls and 208 patients with typical AD (pure AD and Lewy body variant of AD), AD with dementia with Lewy bodies, or typical LBD (dementia with Lewy bodies with amyloid deposition and pure LBD). APOE4 was associated with an increased risk of all disease subtypes except pure LBD. APOE4 was associated with increased frontal β-amyloid burden, and typical LBD was associated with increased occipital β-amyloid levels through its interaction with APOE4. APOE4 was associated with deteriorated general cognition and memory dysfunction via its interaction with typical LBD and AD, respectively. In conclusion, the impact of APOE4 on disease risk depends on its effects on β-amyloid deposition, and APOE4 is associated with β-amyloid deposition regardless of the clinical diagnosis. However, it interacts with typical LBD to cause occipital β-amyloid deposition.


Extravascular red blood cells and hemoglobin promote tumor growth and therapeutic resistance as endogenous danger signals.
Hemorrhage is a common clinical manifestation in patients with cancer. Intratumor hemorrhage has been demonstrated to be a poor prognostic factor for cancer patients. In this study, we investigated the role of RBCs and hemoglobin (Hb) in the process of tumor progression and therapeutical response. RBCs and Hb potently promoted tumor cell proliferation and syngenic tumor growth. RBCs and Hb activated the reactive oxygen species-NF-κB pathway in both tumor cells and macrophages. RBCs and Hb also induced chemoresistance mediated, in part, by upregulating ABCB1 gene expression. Tumor growth induced by RBCs was accompanied by an inflammatory signature, increased tumor vasculature, and influx of M2 macrophages. In both the peritoneal cavity and tumor microenvironment, extravascular RBCs rapidly recruited monocyte-macrophages into the lesion sites. In addition, RBCs and Hb increased several nucleotide-binding oligomerization domain-like receptors' expression and induced IL-1β release. Our results provide novel insights into the protumor function of RBCs and Hb as endogenous danger signals, which can promote tumor cell proliferation, macrophage recruitment, and polarization. Hemorrhage may represent a useful prognostic factor for cancer patients because of its role in tumor promotion and chemoresistance.


Investigation of SARS-CoV-2 Detection Method Applicability and Virus Occurrence in Food and Food Packaging.
While it is clear that SARS CoV-2 coronavirus is the primary respiratory virus, there are no entirely clarified ways of transmission. Foodborne transmission has remained an unexplained path. Therefore, the goals of this paper are to examine and present an assessment of the most appropriate of the four selected kits for RNA extraction for the testing and detection of SARS-CoV-2 on food packaging surfaces, food surfaces, and in food. This will enable to indicate the possibility of infection through contact or direct food consumption. Finding the best technique is vital as RNA extraction is one of the essential elements in detecting SARS-CoV-2. This was achieved through an experiment with four commercial kits following the original manufacturers' protocols, and with a modification of the original protocols that included the use of ethanol and isopropanol. The selected kit was used for RNA extraction from the swabs of packaging surfaces, food surface, and ready-to-eat food samples. The coronavirus was then identified using real-time reverse transcription-polymerase chain reaction (RT-PCR) assays to determine whether the SARS-CoV-2 virus or viral particles are present in the food chain with the overall purpose of demonstrating the possibility that food can contribute as a vehicle for the transmission of the virus. The findings of this investigation made the most effective extraction kit and protocol stand out. The results of the applicability of the kit indicated a significant share of positive samples of viral SARS-CoV-2 virus particles on surfaces from the environment where infected persons with 'silent' COVID-19 infection, with mild symptoms or no symptoms, were present. However, according to the findings of the second part of the study, the virus was not detected on the examined samples of food packaging surfaces, food surfaces, and food. The presented results distinguished one of the most suitable protocols for isolating RNA from environmental surface samples. The main contribution of the study is in the presentation of the results, that is, the examination of samples that are primarily related to the food chain, food packaging, food surfaces, and ready-to-eat food. The results of this study could also be helpful for further determination of the potential of food as a vector for the transmission of coronaviruses.


Acidocalcisome-Mitochondrion Membrane Contact Sites in Trypanosoma brucei.
Membrane contact sites are regions of close apposition between two organelles, typically less than 30 nanometers apart, that facilitate transfer of biomolecules. The presence of contact sites has been demonstrated in yeast, plants, and mammalian cells. Here, we investigated the presence of such contact sites in Trypanosoma brucei. In mammalian cells, endoplasmic reticulum-mitochondria contact sites facilitate mitochondrial uptake of Ca2+ released by the ER-located inositol 1,4,5-trisphosphate receptor (InsP₃R). However, the InsP₃R in trypanosomes localizes to acidocalcisomes, which serve as major Ca2+ stores in these parasites. In this work, we have used super-resolution structured illumination microscopy and electron microscopy to identify membrane contact sites that exist between acidocalcisomes and mitochondria. Furthermore, we have confirmed the close association of these organelles using proximity ligation assays. Characterization of these contact sites may be a necessary starting point towards unraveling the role of Ca2+ in regulating trypanosome bioenergetics.


Significance of Upper Mediastinal Lymph Node Dissection with Video-Assisted Thoracic Surgery in the Treatment of Middle Thoracic Esophageal Carcinoma.
The aim of this study was to explore the significance of upper mediastinal lymph node dissection performed by video-assisted thoracic surgery in the treatment of middle thoracic esophageal carcinoma. The clinical and pathological data from 128 patients with middle thoracic esophageal carcinoma who underwent surgery from January 2013 to December 2015 using a right chest-abdomen-neck approach combined with thoracoscopy and laparoscopy in the Jieyang People's Hospital of Huangdong province were analyzed retrospectively. The lymph node metastasis rates of the thoracic left para-recurrent laryngeal nerve (1, 2, and 4L zones) and right para-recurrent laryngeal nerve (1R zone) were 30.47% and 28.12% in 128 cases, respectively. The metastasis rates of the 2R, 4R, and 5 zones were 4.69%, 3.91%, and 5.47%, respectively. The upper mediastinal region was the most common location for lymph node metastasis from middle thoracic esophageal carcinoma, and upper mediastinal lymph node dissection performed by video-assisted thoracic surgery was safe and complete. It also reduced the risk of para-recurrent laryngeal nerve injury, residual tumor, and the postoperative recurrence rate.


The clothes maketh the sign.
Pattern recognition is a key tool that enables radiologists to evoke certain diagnoses based on a radiologic appearance. In Shakespeare's Hamlet, Polonius tells his son Laertes to dress well because "apparel oft proclaims the man"; this phrase is now expressed in modern parlance as "the clothes maketh the man". Similarly in radiology, appearances are everything, and in the case of radiologic signs, occasionally "the clothes maketh the sign". The radiologic signs described in this pictorial review resemble items of clothing, fabric types, headwear, or accessories and are found in the musculoskeletal, pulmonary, gastrointestinal, and genitourinary systems. These "clothing signs" serve as a useful visual trigger to help radiologists to identify particular disease entities. • Pattern recognition enables radiologists to evoke a diagnosis based on radiologic appearance. • The radiologic signs described in this review resemble clothing, fabric, or accessories. • These "clothing signs" serve as visual triggers that evoke particular disease entities.


Utility of objective measures of activity and attention in the assessment of therapeutic response to stimulants in children with attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder that can respond dramatically to medication, if dose is appropriately titrated. Studies suggest that computer measures of attention cannot be used for titration as they show improvement on doses too low to produce clinical benefits. We assessed whether measures of motor activity and attention using the McLean Motion Attention Test (M-MAT) could identify doses associated with optimal clinical response. Eleven boys (9.6 +/- 1.8 years), receiving treatment with methylphenidate, and meeting DSM-IV criteria for ADHD, participated in this triple-blind (parent, child, rater), within-subject, efficacy study. Subjects received 1 week each of placebo, low (0.4 mg/kg), medium (0.8 mg/kg), and high (1.5 mg/kg) daily doses of methylphenidate. Parents rated response using an index of clinical global improvement. In 9/11 subjects, the dose that produced the best improvement on M-MAT measures was also the dose that produced the best clinical outcome (p < 10(5)). Parents rated response to this dose significantly better than response to previously prescribed treatment. Objective measures of primarily activity and secondarily attention responded to treatment in a manner concordant with clinical ratings, suggesting that these measures have ecological validity, and the potential to facilitate medication management and titration.


Defective vaccine-induced immunity to Schistosoma mansoni in P strain mice. I. Analysis of antibody responses.
Inbred P4 strain mice have previously been shown to be uniquely defective in their resistance to challenge infection induced by irradiated cercariae of Schistosoma mansoni. To assess whether the low levels of resistance developed by vaccinated P mice could be due to a defective antibody response, we compared the anti-schistosomulum antibody responses in vaccinated P animals with those occurring in vaccinated C57BL/6J (B6) mice, a strain that consistently develops high levels of resistance to challenge infection. Our results indicate that vaccinated P mice develop levels of total anti-schistosomulum antibodies that are significantly lower than those occurring in B6 mice for at least 15 wk after immunization, with the exception of the fifth week, at which time the responses are indistinguishable. Further analysis revealed that the defect in P strain antibody response occurs specifically in the IgM isotype and that specific IgM levels in P mice are less than one-half the levels in B6 mice at every time point examined. In contrast, no differences in total IgM immunoglobulins were evident when sera from normal (nonvaccinated) P and B6 mice were compared. P mouse anti-schistosomulum IgG antibody responses reached the same levels as those observed in B6 mice by 5 wk after vaccination. However, a much faster decay in IgG antibody levels occurred after this time point in P animals. No differences were observed when the levels of anti-schistosomulum antibodies occurring in each of the major IgG isotypes (IgG1, IgG2a, IgG2b, IgG3) were compared in sera from P and B6 mice vaccinated 4 wk previously. Similarly, vaccinated P and B6 mice were found to mount indistinguishable IgG anamnestic responses after challenge infection. Finally, no differences between vaccinated P and B6 mice were observed when immediate (30 min) skin test and mast cell degranulation responses to a soluble schistosome antigenic preparation were compared. The above findings suggest that P strain mice have a specific defect in their ability to mount IgM antibody responses after immunization with irradiated cercariae. The possible contribution of this defect in IgM response to the decreased resistance of vaccinated P mice to challenge infection is discussed.